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Updated: Sep 21, 2025
Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS
Published on: August 10, 2017
Bioevaluation of a dual PI3K/HDAC inhibitor for the treatment of diffuse large B-cell lymphoma
Kehui Zhang1, Lei Huang2, Fangfang Lai2
1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; CAMS Key Laboratory of Small Molecule Immuno-Oncology Drug Discovery, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Abstract:
The synergistic anti-tumor effect by simultaneous inhibitions of PI3K and HDAC has been verified to provide the rationality of PI3K/HDAC dual inhibitors for cancer treatment. Notably, the outstanding effect of PI3K/HDAC dual inhibitors against DLBCL has been paid much attention, especially for RR-DLBCL. Our previously reported 4-methylquinazoine scaffold based PI3K/HDAC dual inhibitors could suppress the growth of solid tumors and hematologic malignancies both in vitro and in vivo, validating the potential as new therapeutic agents for cancer. In this research, we further investigated the anti-tumor activity of one of our compounds against DLBCL cell lines and in vivo zebrafish xenograft model as well as the underlying mechanism, hoping to provide a novel therapeutic agent for treating DLBCL.
Insights
Dual inhibitors targeting PI3K and HDAC show promise for treating Diffuse Large B-cell Lymphoma (DLBCL). This study investigated a novel compound
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Simultaneous inhibition of Phosphoinositide 3-kinase (PI3K) and Histone Deacetylase (HDAC) demonstrates synergistic anti-tumor effects, supporting the development of dual PI3K/HDAC inhibitors for cancer therapy.
- PI3K/HDAC dual inhibitors have shown significant efficacy against Diffuse Large B-cell Lymphoma (DLBCL), particularly relapsed/refractory DLBCL (RR-DLBCL).
- Previously developed 4-methylquinazoine scaffold-based PI3K/HDAC dual inhibitors have exhibited potent anti-cancer activity against both solid tumors and hematologic malignancies in vitro and in vivo.
Purpose of the Study:
- To investigate the anti-tumor activity of a specific 4-methylquinazoine scaffold-based PI3K/HDAC dual inhibitor against DLBCL.
- To elucidate the underlying anti-cancer mechanisms of the compound in DLBCL.
- To evaluate the compound's efficacy in DLBCL cell lines and an in vivo zebrafish xenograft model.
Main Methods:
- In vitro studies using DLBCL cell lines.
- In vivo evaluation using a zebrafish xenograft model.
- Mechanistic studies to understand the compound's mode of action.
Main Results:
- The compound demonstrated significant anti-tumor activity against DLBCL cell lines.
- In vivo studies in the zebrafish xenograft model confirmed the compound's efficacy.
- Mechanistic investigations provided insights into the compound's anti-cancer effects.
Conclusions:
- The investigated PI3K/HDAC dual inhibitor exhibits promising therapeutic potential for treating DLBCL.
- This compound represents a potential novel therapeutic agent for DLBCL patients.
- Further research is warranted to advance this compound towards clinical application.
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